Figure 5.

Transposon-mediated cancer gene discovery screen. Breeding of 'jumpstarter' and 'mutator' stocks induces transposition in the soma of double-transgenic animals ('oncomice'). In the case of tissue-specific screens, a third genotype containing a tissue-specific Cre allele has to be crossed in to the backgrounds. The crosses can be made either in wild-type or in specific cancer-predisposed genetic backgrounds. Transposition in somatic cells leads to random insertional mutations, and animals are monitored for tumor development. Transposon insertions are cloned from genomic DNA isolated from tumor samples, and are subsequently mapped and the mutagenized genes identified. Those genes repeatedly mutated in multiple, independent tumors are designated as common insertion sites (CIS). These candidate cancer genes are then functionally validated.